RADIOIMMUNOASSAY OF ANTARELIX(TM), A LUTEINIZING-HORMONE RELEASING-HORMONE ANTAGONIST, IN PLASMA AND ITS APPLICATION FOR PHARMACOKINETIC STUDY IN DOGS

A procedure for the radioimmunoassay (RTA) of Antarelix(TM) (teverelix ) in plasma has been developed for the pharmacokinetic study of this p otent LHRH antagonist in dogs. Antiserum was produced by coupling the deamidated Antarelix analog to bovine serum albumin by a carbodiimide reaction and immunizing rabbits with the conjugate. The crossreactivit y of the antiserum with LHRH, LHRH agonist Metereline and LHRH antagon ists tested was negligible, except for Antide which displayed a crossr eactivity of 33%. No crossreactivity with Antarelix metabolites could be detected. The RTA is suitable for the direct determination of Antar elix in plasma, with a minimum detectable level of 1.12 fmol/assay. Th e accuracy and precision of the method were assessed with plasma sampl es spiked with Antarelix at concentrations ranging from 0.4 to 6.4 pmo l/ml. The recovery was 104.8% with intra- and interassay CV between 1 and 3.7%. Pharmacokinetic profiles of Antarelix in dogs were establish ed following an IV or a SC dose of 10 mu g/kg.